Module 1: Microorganisms

Introduction
A disease is an interruption, cessation, or disorder of body functions.  In other words, part or all of the body is incapable of carrying on its required functions.

There can be many direct causes of disease, including:

• • • disease-producing organisms
    • chemicals
    • physical agents
    • malnutrition
    • genetic defects
    • degeneration
    • neoplasms*

This course is focused on infectious diseases.  In this module, you will learn about the various types of microorganisms which are normally present in humans, and microorganisms which are common infectious agents in disease.

Module Structure
This module is divided into two sections:

Section 1:  Microorganisms
Section 2:  Normal Flora

Learning Objectives
After reading this section, you should be able to:

1. Define the terms infectious disease, pathogen, and parasite.
2. Describe the structure of a virus.
3. Explain how viruses replicate.
4. Name the three types of bacteria based on shape.
5. Differentiate between Gram-positive and Gram-negative bacteria and give two common examples of each.
6. Differentiate between aerobic, anaerobic, and facultative anaerobic bacteria.
7. Describe the basic characteristics of chlamydiae, rickettsiae, and mycoplasmas.
8. Describe the basic characteristics of fungi.
9. List four types of protozoa.
10. List two classes of helminths.
11. State the medical significance of arthropods with respect to infectious disease.

Infectious Disease
Infectious diseases are those diseases caused by the invasion of the body by disease-producing microorganisms.  Most microorganisms are single-celled and quite simple in structure.  They are also referred to as microbes.

Disease-causing organisms are called pathogens*.  If pathogens invade the body, begin to multiply, and produce adverse effects, the condition is called an infection*.

If an organism lives on or in another organism (host) at the host’s expense, it is called a parasite*.  Infection is the process whereby a parasite enters into a relationship with a host.

Endogenous Microorganisms (Normal Flora)
Many organisms normally grow on and in the body and are harmless to the body.  They makeup the body’s normal flora*.  Normally, these endogenous* microorganisms are nonpathogenic, and they usually provide protection against overgrowth of other infective microbes.

However, if a person is in a weakened state due to disease, injury or malnutrition, some microorganisms that are normally harmless may cause an infection.  This is called an opportunistic infection*.

Types of Infectious Agents
Infectious agents that affect humans can be grouped into 4 classes based on their cellular complexity.  See Table 1.1-1.

Viruses
1) Structure
Viruses are quite small (from 10 nm to 300 nm).  (One nanometer (nm) is “one-millionth” of a millimeter.)  They are composed of a core which contains ribonucleic acid (RNA)* or deoxyribonucleic acid (DNA)* surrounded by a protein coat or capsid* (see Figure 1.1-1).  The capsid may contain many protein subunits (capsomeres*) which give the virus a characteristic shape.  The nucleic acid core, capsomere and capsid make up the unit called a nucleocapsid*.

For some viruses, the nucleocapsid is again surrounded by a protein envelope.  The complete intact infecting viral particle is called a virus.

Viruses lack both the enzyme system necessary for energy production and the ribosomes essential for protein synthesis.  Therefore, they cannot survive by themselves.  They must live inside living cells whose biochemical apparatus they utilize for their existence.

2) Classification
Hundreds of viruses are infectious for humans.  There is no universally accepted classification of viruses.  They can be grouped according to:

• • • morphology (size and shape)
    • whether they contain RNA or DNA, and
    • whether or not an envelope and/or capsid is present

See Table 1.1-2 for a list of viral classification.

3) Identification
Due to their small dimensions, viruses are not able to be stained or detected under light microscopy, making isolation and identification difficult.  Organism identification also requires a certain amount of expertise and time.  Therefore diagnosis of viral infection is made only on the clinical presentation and changes in antibody* and antigen* titres.  See Table 1.1-3.

4) Replication
A virus initially attaches to specific receptor sites on the cell membrane of the host before subsequently penetrating the cell.  Once encapsulated in the host’s cell, the protein coat of the virus is dissolved by the host’s enzymes, freeing the genetic material of the virus.  This genetic material then replicates and viral proteins are synthesized.  Subsequently, the components assemble to form a mature virus particle and the DNA or RNA usually becomes encapsulated by viral proteins.  The virus is released from the host cell, which may be lysed and die.  The virus is then free to attach to the membrane of another host cell and begin the procedure once again.

Bacteria
Bacteria (singular bacterium) are microscopic one-celled organisms characterized by the lack of membrane-bound DNA.  Most bacteria are composed of a cell membrane and cell wall.  They contain the biochemical apparatus required to support their own reproduction and survival.

Bacteria are able to cause damage to body cells by producing poisons, or toxins*, and by entering the cells and growing within them.

Several attributes of bacteria are used in their classification.

1) Morphology
Bacteria are classified according to three basic shapes.  Bacteria having a spherical shape are called cocci* (singular coccus).  Cocci can associate in different formations.  Diplococci* are arranged in pairs, streptococci* are arranged in chains, and staphylococci* look like a bunch of grapes.  Rod-shaped bacteria or bacilli* (singular bacillum) are straight and slender.  Spiral-shaped bacteria are called spirochetes*.  Vibrios are curved rod-shaped organisms with a single flagellum*.

2) Staining characteristics
There are various staining procedures employed in bacterial identification.  The Gram stain is most commonly used because it is easy to perform and is inexpensive.  It categorizes bacteria as being Gram-positive* or Gram-negative*.

The bacterial wall differs in composition between Gram-negative and Gram-positive bacteria.  Gram-negative bacteria have an additional outer membrane which provides greater resistance against many antibiotics.

Gram-positive bacteria retain violet stain and appear purple.  Gram-negative bacteria do not retain violet stain and are counterstained to appear pink.

3) Oxygen tolerance
Bacteria also differ in their ability to tolerate or grow in the presence or absence of oxygen.  Anaerobes* will grow only in complete absence of oxygen.  Aerobes* will grow only in the presence of oxygen.

Facultative anaerobes* can grow either in the presence or absence of oxygen.  Most bacteria demonstrate facultative characteristics.

Most of the pathogens causing infectious disease are bacteria.  See Table 1.1-4 for a list of common diseases caused by bacteria.

Table 1.1-5 lists common Gram-positive and Gram-negative bacteria.

Chlamydiae and Rickettsiae
Chlamydiae and rickettsiae are usually classified as bacteria, although they are considerably smaller.  They can only exist inside living cells.  Table 1.1-6 lists some common diseases caused by chlamydiae and rickettsiae.

1) Chlamydiae
Chlamydiae possess a cell wall.  They can make their own DNA, RNA and protein but are unable to produce their own energy sources.  They rely on the host for replication, similar to viruses, but are more closely related to Gram-negative bacteria than to viruses.

2) Rickettsiae
Rickettsiae possess a cell wall that is structurally and biochemically similar to the Gram-negative cell wall.

Their natural hosts are the arthropods (lice, mites, ticks, fleas), where they multiply without often producing disease.  However, when transmitted to humans, they may cause disease.

Mycoplasmas
Mycoplasmas are the smallest living entities that can grow independently of the host cell.  Some are smaller than the average virus.

Mycoplasmas are Gram-negative organisms without cell walls.  As a result, they are not susceptible to antibiotics that affect the integrity of the bacteria cell wall (e.g. penicillins).  However, they are inhibited by tetracycline, antibiotics, and by macrolide antibiotics such as erythromycin, clarithromycin and azithromycin.

One common species of this group is Mycoplasma pneumoniae which causes an atypical pneumonia.

Fungi
Fungi are plantlike organisms.  Fungal cells contain a nucleus, cytoplasmic organelles, a cytoplasmic membrane cell wall, mitochondria and endoplasmic reticulum.  The cytoplasmic membrane is made up of sterols which are the target of most antifungal drugs.  Because fungi lack the pigment required to produce energy by photosynthesis, they require an exogenous* organic energy source to sustain life.

They range in size from nonvisible structures to visible ones and vary from simple to very complex colonies of organisms.  Single-celled fungi are called yeasts*.  Yeasts are formed when a bud, which extends out from a round or oblong parent, constricts to form a new cell.  Another type of fungi, the molds*, are intricate large structures made up of intertwined networks of elongated tubelike structures.  In general, diseases in humans are caused by the yeast forms.

Any disease caused by a fungus is termed mycosis*.

Fungal infections can be classified into three major clinical types of diseases: Superficial, opportunistic and systemic infections.  See Table 1.1-7.  Superficial infections involve the nails, hair, or skin.  Opportunistic infections occur in an immunocompromised host (e.g. persons with AIDs, cancer, diabetes).  Systemic infections affect the whole body.

Protozoa
Protozoa of medical importance are unicellular, non-photosynthetic cells that lack cell walls.  They have a nucleus with chromosomes.  They also contain many membrane-bound compartments (organelles) in which cellular functions are performed.

There are four main types of protozoa, based on their morphology:

1) Amebas
Amebas have no definite shape.  They propel themselves by extending a “false foot” (pseudopod) and then flowing into the extension.

2) Ciliates
Ciliates are covered with tiny hairs called cilia* which help propel the organism.

3) Flagellates
Flagellates are propelled by long, whiplike tails called flagella*.

4) Sporozoa
Sporozoa cannot propel themselves.  They are unable to grow outside a host.

Examples of infectious protozoal diseases are listed in Table 1.1-8.

Helminths
Helminths, more commonly known as parasitic worms, are multicellular organisms.  There are numerous worms that are medically important.  The two main classifications include flatworms and roundworms.

Examples of flatworms include tapeworms and flukes.

An example of a roundworm (nematode*) is the pinworm which lives in the large intestine.

The consequences of helminth infections vary from no clinical manifestations to severe disease, depending on the species, the number of worms in the body of the host and the host defenses.

Arthropods
Arthropods are organisms that have a hard, jointed exoskeleton and paired, jointed appendages.  They are important medically because they infest* the human skin or serve as a vector in the transmission of other pathogens.

Some examples of arthropods include the scabies mite, the head and body louse, and the crab louse.

Common Infection Diseases
Almost every body tissue and organ may be affected by an infectious agent.  See Table 1.1-9 for a summary of the pathogens associated with common infection diseases.  We discuss these diseases in more detail in other modules of the course.

Summary — Section 1: Microorganisms

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Infectious diseases are caused by an invasion of the body by disease-producing microorganisms such as:

• • • viruses
    • bacteria — cocci, bacilli, spirochetes
    • chlamydiae
    • rickettsiae
    • mycoplasmas
    • fungi — yeasts, molds
    • protozoa — amebas, ciliates, flagellates, sporozoa
    • helminths — flatworms, roundworms

Most of the pathogens which cause infectious diseases are bacteria.  The Gram stain is most commonly used to identify bacteria.  Gram-negative bacteria are more resistant than Gram-positive bacteria to many antibiotics due to the presence of an outer membrane.  Aerobic bacteria require oxygen in order to grow, while anaerobic bacteria will only grow in the absence of oxygen.  Facultative anaerobes grow either in the presence or absence of oxygen.  Most bacteria demonstrate facultative characteristics.

Viruses must live inside a host as they are unable to synthesize proteins or produce energy themselves.  Due to their small size, diagnosis of viral infection is based on clinical presentation and changes in antibody and antigen titers.

Chlamydiae and rickettsiae can only exist inside living cells and are usually classified as bacteria, although they are considerably smaller.

Mycoplasmas can grow independently of a host cell.  They are Gram-negative organisms without cell walls.

Fungi are plantlike organisms.  They are unable to produce their own energy by photosynthesis.  Most diseases in humans are caused by yeasts rather than molds.

Many pathogenic protozoa are unicellular, non-photosynthetic cells that lack cell walls.

Helminths are parasitic worms such as tapeworms, flukes, and nematodes.

Arthropods such as mites or ticks may infest the skin or transmit pathogens by biting the host.

Progress Check — Section 1: Microorganisms

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1.

Infectious diseases are caused when ______________________ invade the body.

2.

Define the following terms:

1) pathogen
______________________________________
2) parasite
______________________________________

3.

A virus is composed of a nucleic acid core containing _________________________ or ____________________, and a capsid containing _________________________.

4.

Explain how a virus replicates.
_____________________________________
_____________________________________
_____________________________________
_____________________________________

5.

Describe the shape of each of the following types of bacteria:

1) cocci _______________________________
2) bacilli ______________________________
3) spirochetes ___________________________

6.

Explain how the cell wall of Gram-negative bacteria differs from that of Gram-positive bacteria.
__________________________________
__________________________________
__________________________________
__________________________________

7.

Bacteria, which grow only in the presence of oxygen, are called  _________________. Those, which grow only in the absence of oxygen, are called ____________________.

8.

Chlamydiae and rickettsiae are usually classified as ____________________because their cell wall is similar to that of ______________________.

9.

Many fungal diseases are caused by single celled fungi called __________________.

10.

List the 4 main types of protozoa.
1) _______________________
2) _______________________
3) _______________________
4) _______________________

11.

Parasitic worms are called ______________________.

12.

Why are arthropods important medically?
________________________________________
________________________________________
________________________________________
________________________________________

 

Progress Check Answers — Section 1: Microorganisms

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1.

microorganisms

2.

1) disease causing organism
2) oganism which lives on or in another organism at host’s expense

3.

RNA or DNA
capsomeres

4.

The virus attaches to specific receptor sites on the host.
The virus penetrates the cell.
Once the protein coat of the virus is dissolved, the viral genetic material replicates and viral proteins are synthesized.
The virus is released from the host cell.
The host cell is lysed and dies

5.

1) spherical
2) rod-shaped
3) spiral

6.

The Gram-negative bacterial cell wall has an additional outer membrane which provides greater resistance against many antibiotics.

7.

aerobes
anaerobes

8.

bacteria
Gram-negative bacteria

9.

yeasts

10.

The four main types of protozoa are:

1) amebas
2) ciliates
3) flagellates
4) sporozoa

11.

helminths

12.

Arthropods are able to infest the skin or transmit pathogens by inoculating the host after a bite.

Section 2: Normal Flora

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Learning Objectives
After reading this section, you should be able to:

1. Identify bacterial organisms native to different sites of the human body.
2. List 3 factors that may alter normal flora in the human host.

Normal Flora
Many microorganisms are normal flora that naturally inhabit internal and external surfaces of the healthy human host.

The type and numbers of normal flora depend on:

• • • body site
    • age
    • diet
    • disease

Normal flora can also be affected by factors such as hospitalization.  When hospitalized, the human host may become colonized with bacteria that are not usually present as normal flora.  These bacteria do not usually result in infection.  Antibiotic use can inhibit the growth of endogenous flora and allow the overgrowth of other bacteria.

Under normal circumstances, endogenous flora are nonpathogenic and can even be beneficial.  For example, gastrointestinal bacteria produce vitamin K, aid nutrient absorption and prevent invasion of pathogenic microorganisms.

In some cases, however, normal flora can become pathogenic.  For example, endogenous flora from one site (i.e., skin, gastrointestinal tract) can be introduced through disease or trauma into otherwise sterile areas (i.e., blood, central nervous system).

Immunocompromised* patients can be more susceptible to infections caused by normal flora.

Skin
The skin is usually colonized by Gram-positive aerobic and some anaerobic bacteria.

• • • Staphylococcus epidermidis — found on the skin in all individuals
    • Diphtheroids — found on the skin in 55% of individuals
    • Staphylococcus aureus — found on the skin in 5% in 25% of individuals
    • Propionibacterium acnes (45% to 100%) and Clostridium perfringens (40% to 60%) — found in deep sebaceous glands in the skin

Although the presence of Gram-negative bacteria on the skin is unusual, colonization may occur following hospitalization, especially in patients admitted to an intensive care unit.

A break in the skin as a result of trauma, intravenous catheters or surgery may introduce normal skin flora into the systemic circulation and cause infection.  Staphylococcus aureus and Staphylococcus epidermidis are the most common normal skin flora isolated from blood cultures.

Nose and Nasopharynx
The most common bacteria found in the nose (usually in highest numbers just inside the nares) are:

• • • staphylococci
    • diphtheroids
    • streptococci
    • Haemophilus
    • Neisseria

Mouth
The microbial flora of the mouth show marked interpatient variation, depending upon oral hygiene and health.

In children, Streptococcus sanguis and Streptococcus mutans predominate.

In adults, Staphylococcus epidermidis, Staphylococcus aureus and Streptococcus species are commonly found.

Dental caries and advanced dental disease can significantly increase the numbers of Streptococcus mutans and anaerobes in the mouth.  Poor mouth care predisposes patients to periodontal infections and, potentially, aspiration pneumonia.

Stomach
Under ordinary circumstances, the stomach has few viable microorganisms.  Acid is the primary inhibitor of bacterial growth in the stomach.  Reduced acidity due to age, disease or drugs (i.e., antacids, histamine-2 receptor antagonists, proton pump inhibitors) can increase the number of stomach microorganisms.

Small Intestine
The upper portion of the small intestine contains few bacteria.  When present, Gram-positive cocci and bacilli predominate.  Streptococci, enterococci, lactobacilli and diphtheroids are occasionally found in the jejunum and upper ileum, but are more common in the lower ileum.  The presence of disease such as obstruction or diverticulitis can introduce bacteria to the site and alter the normal flora.

Large Intestine
The colon has the largest microbial population in the body.  The number of microorganisms in stool approaches an estimated 10¹² organisms per gram of contents.  These microorganisms consist primarily of:

• • • Gram-negative anaerobes (Bacteroides, Fusobacterium)
    • diphtheroids
    • enterobacteraciae ( coli, Enterobacter, Klebsiella)
    • enterococci
    • staphylococci

Genitourinary Tract
The urinary tract including kidneys, bladder and ureters are usually sterile sites without normal flora.  Some bacteria (i.e., staphylococci, diphtheroids) may be present in the distal urethra of both females and males.

The adult female genital tract has complex normal flora that can change with the menstrual cycle.  Lactobacilli and Bacteroides species are the most prevalent microorganisms.  Other organisms that are capable of proliferating at the low pH of the female genital tract include enterococci, Candida albicans and large numbers of anaerobic bacteria.  The cervicovaginal canal can also have anaerobic Gram-positive cocci, Gram-negative bacilli and clostridia, however, most organisms are not capable of growth in the low pH of the vagina and are of little medical significance.

Summary — Section 2:  Normal Flora

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Many microorganisms are commonly found in the body.  Under normal circumstances, endogenous flora are nonpathogenic and can even be beneficial.  In some cases, however, normal flora can become pathogenic.

The skin is usually colonized by Gram-positive aerobic and some anaerobic bacteria.  The nose contains a variety of bacteria, with the highest numbers being  just inside the nares.  Oral hygiene and dental health affect the flora of the mouth.  The stomach usually has few viable microorganisms due to its acidic environment.  The upper part of the small intestine also contains few bacteria.  The large intestine has the largest number of microorganisms.  The urinary tract usually has no microorganisms present.  The adult female genital tract has normal flora present that may change with the menstrual cycle.

Progress Check — Section 2:  Normal Flora

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1.

Indicate whether each of the following statements is True or False.

2.

List 3 factors that may alter normal flora in humans.
1) __________________________________
2) __________________________________
3) __________________________________

Progress Check Answers — Section 2:  Normal Flora

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1.

1) False
Normal flora are harmless bacteria normally found in or on the human host.
2) True
3) True
4) True
5) False
The large intestine is most heavily colonized with Bacteroides species.
6) False
The female genital tract is most commonly colonized with Lactobacillus and Bacteroides species.

2.

Any 3 of the followiong may alter normal flors:

1) hospitalization (IV catheters, surgery)
2) antibiotics
3) disease or trauma
4) dental caries and disease
5) altered pH

Module 1 Test: Microorganisms

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1.

Which of the following microorganisms are composed of a nucleic acid core, capsid and protein envelope?

a) viruses
b) fungi
c) bacteria
d) helminths

2.

Which of the following microorganisms are classified using the Gram stain?

a) helminths
b) bacteria
c) arthropods
d) fungi

3.

Which of the following microorganisms are classified as yeasts or molds?

a) fungi
b) viruses
c) protozoa
d) helminths

4.

What shape are cocci?

a) worm-like
b) rod shaped
c) round shaped
d) spindle shaped

5.

An example of a common Gram-positive bacteria is:

a) Escherichia coli
b) Pseudomonas aeruginosa
c) Bacteroides fragilis
d) Staphylococcus aureus

6.

Aerobic bacteria:

a) require oxygen
b) do not require oxygen
c) produce oxygen
d) produce spores

7.

Normal flora are bacteria in the human host that are typically:

a) pathogenic
b) invasive
c) harmless
d) contagious

8.

Normal flora are not present:

a) on the skin
b) in the large intestine
c) in the urinary tract
d) in the mouth

9.

The highest number of normal flora are present:

a) on the skin
b) in the large intestine
c) in the cerebral spinal fluid
d) in the mouth

10.

The skin is most commonly colonized with:

a) Candida spp
b) staphylococci
c) Bacteroides spp
d) Klebsiella

Module 1 test Answers: Microorganisms

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1.

a) virus

2.

b) bacteria

3.

a) fungi

4.

c) round shaped

5.

d) Staphylococcus aureus

6.

a) require oxygen

7

c) harmless

8.

c) in the urinary tract

9.

b) in the large intestine

10.

b) staphylococci